Animal models are an important aspect vaccine development. Chimpanzees can be infected with HIV-1, however they do not develop AIDS. Secondly, the total number of Chimpanzees available for research is small. Recently, rabbits have been show to become infected with HIV-1. Rabbits could provide a useful model for early safety and toxicity tests of candidate AIDS vaccines and may provide some indication of immunogenicity for some of the potential immunogens, as well. We inoculated one rabbit each with one of the following HIV-1 strains: IIIB, RF, Mn, Zaire, and BR. We looked at the development of infection by analyzing sera by Western blot and ELISA, and culturing lymphocytes and monitoring the cultures for reverse transcriptase and HIV-1 antigen production. Lymphocytes were also tested for provirus using the polymerase chain reaction (PCR). At necropsy, the brain, lymphocytes, lymph node, sacculus rotundus, spleen, and thymus were collected for culture and for testing by the PCR. In addition, these tissues were examined histopathologically. Our results indicate that the five strains of HIV-1 infected rabbits variably, unrelated to inoculum titer. Only the strains RF and Mn induced detectable antienvelope antibodies. Of the tissues tested the lymphocytes and lymph node were often positive for virus. None of the rabbits showed signs of immune deficiency, and the tissues examined were normal histologically. The differences observed between the HIV-1 strains in rabbits may yield important models of pathogenesis of these different HIV-1 strains.